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Zhu Z, Shen W, Hu J, Jin M, Shi L, Wu Y, Fan J. Risk factors for latent tuberculosis infection clustering among the elderly: a population-based cross-sectional study in Eastern China. BMC Infect Dis 2025; 25:368. [PMID: 40098074 PMCID: PMC11912638 DOI: 10.1186/s12879-025-10743-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 03/04/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Tuberculosis (TB) remains a major global health threat. Mass screening effectively detects hidden TB cases and latent tuberculosis infections (LTBI), crucial for prevention. This study aims to use IFN-γ release assay (IGRA) screening in Deqing elderly reveals hidden TB and LTBI cases, explore the risk factors influencing the clustering of LTBI. METHODS A cross-sectional study was conducted in 2023 among elderly residents (aged 60 years or above) in Deqing County using IGRA test (AIMTB). Participants were sampled from 13 towns or sub-districts proportional to their populations (26,234 participants, 19.01% of the elderly population aged 60 and above in Deqing). Demographic information and comorbidities were collected. Spatial autocorrelation analysis was conducted at the village level to identify LTBI clusters, and logistic regression was used to explore clustering risk factors by comparing population characteristics in hot spots versus cold spots. RESULTS Of the 26,234 participants, 25,952 with complete data and definite IGRA results were included in the analysis. 1,878 were diagnosed with LTBI, resulting in an overall prevalence of 7.34%. LTBI prevalence was higher in males (8.69% vs. 6.01%, P < 0.0001), those aged over 70 and 80 (8.80% vs. 7.24% vs. 6.66%, P < 0.001), and individuals with low or high BMI (8.06% vs. 7.91% vs. 6.75%, P < 0.0001), smokers (8.89% vs. 6.77%, P < 0.001), and alcohol consumers (8.77% vs. 6.77%, P < 0.0001). Spatial analysis revealed 18 villages as cold spots and 5 as hot spots. Multivariable logistic regression of cold and hot spots identified age (70-79) (OR = 1.550, 95% CI = 1.225-1.962, P < 0.001) and alcohol consumers (OR = 1.495, 95% CI = 1.139-1.967, P = 0.004) are clustering risk factors. BMI (< 18.5) (OR = 0.451, 95%CI = 0.319-0.637, P < 0.001), and literate are clustering protective factors (OR = 0.556, 95%CI = 0.425-0.727, P < 0.001). CONCLUSION This study underscores the high burden of LTBI among elderly males and individuals with certain risk factors in Deqing County. Identifying age and alcohol consumers as key factors in LTBI clustering suggests targeted interventions in high-risk villages could enhance TB prevention and control efforts.
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Affiliation(s)
- Zhenguo Zhu
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Wei Shen
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Jiajun Hu
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Meng Jin
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Lijie Shi
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Yafang Wu
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China
| | - Jianliang Fan
- County Health Inspection Office, Deqing County Center for Disease Prevention and Control, Deqing county, 313200, Zhejiang province, China.
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Karur AK, Kumar P, Nayak-Rao S. Lessons for the clinical nephrologist: a rare presentation of extrapulmonary tuberculosis in a hemodialysis patient. J Nephrol 2025:10.1007/s40620-024-02183-4. [PMID: 39903383 DOI: 10.1007/s40620-024-02183-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 11/27/2024] [Indexed: 02/06/2025]
Affiliation(s)
- Athish Kannan Karur
- Department of Nephrology, Sri Devaraj Urs Academy of Higher Education and Research, Tamaka, Kolar, Karnataka, 563103, India
| | - Prasanna Kumar
- Department of Nephrology, Sri Devaraj Urs Academy of Higher Education and Research, Tamaka, Kolar, Karnataka, 563103, India
| | - Shobhana Nayak-Rao
- Department of Nephrology, Sri Devaraj Urs Academy of Higher Education and Research, Tamaka, Kolar, Karnataka, 563103, India.
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Prasad P, Sharma S, Mohanasundaram S, Agarwal A, Verma H. Tuberculosis in kidney transplant candidates and recipients. World J Transplant 2024; 14:96225. [PMID: 39295970 PMCID: PMC11317863 DOI: 10.5500/wjt.v14.i3.96225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/06/2024] [Accepted: 07/04/2024] [Indexed: 07/31/2024] Open
Abstract
Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.
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Affiliation(s)
- Pallavi Prasad
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | - Sourabh Sharma
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | | | - Anupam Agarwal
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
| | - Himanshu Verma
- Department of Nephrology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, Delhi, India
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Abdullah, Behera MR, Kaul A, Agarwal V, Prasad P, Prasad N, Bhadauria DS, Patel MR, Sharma H. The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients. Int J Mycobacteriol 2024; 13:183-190. [PMID: 38916390 DOI: 10.4103/ijmy.ijmy_33_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 04/12/2024] [Indexed: 06/26/2024] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.
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Affiliation(s)
- Abdullah
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Manas Ranjan Behera
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anupma Kaul
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Vikas Agarwal
- Department of Clinical Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Pallavi Prasad
- Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Narayan Prasad
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Dharmendra Singh Bhadauria
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Manas Ranjan Patel
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Harshita Sharma
- Department of Nephrology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Canney M, Gunning HM, Johnston JC, Induruwage D, Zheng Y, Barbour SJ. Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study. Am J Kidney Dis 2023; 82:725-736. [PMID: 37516296 DOI: 10.1053/j.ajkd.2023.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 04/16/2023] [Accepted: 05/18/2023] [Indexed: 07/31/2023]
Abstract
RATIONALE & OBJECTIVE Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. STUDY DESIGN Observational cohort study. SETTING & PARTICIPANTS A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. EXPOSURE Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. OUTCOME A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. ANALYTICAL APPROACH The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. RESULTS The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). LIMITATIONS A relatively low number of events contributed to uncertainty in risk estimates. CONCLUSIONS Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. PLAIN-LANGUAGE SUMMARY Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.
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Affiliation(s)
- Mark Canney
- Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario
| | - Heather M Gunning
- Division of Nephrology, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - James C Johnston
- Division of Respiratory Medicine, Vancouver, British Columbia, Canada; British Columbia Centre for Disease Control (JCJ), Vancouver, British Columbia, Canada
| | - Dilshani Induruwage
- Department of Medicine, University of British Columbia, BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Yuyan Zheng
- Department of Medicine, University of British Columbia, BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Sean J Barbour
- Division of Nephrology, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada.
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Oshima S, Sakuragi M, Morita H, Oka Y, Tabu H, Marumo S, Suzuki H, Tsukamoto T. Successful treatment of tuberculous meningitis in an Indian female under hemodialysis therapy. CEN Case Rep 2023; 12:341-346. [PMID: 36611090 PMCID: PMC10620348 DOI: 10.1007/s13730-022-00771-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 12/21/2022] [Indexed: 01/09/2023] Open
Abstract
Hemodialysis is a well-known risk factor for severe infection by putting patients under an immunocompromised state. Such patients are prone to opportunistic pathogen and present with atypical manifestations during infection. Tuberculous meningitis is a central nervous system infection of Mycobacterium tuberculosis, accounting for the highest mortality of all forms of tuberculosis. In fact, the mortality rate of tuberculous meningitis in hemodialysis patients is extremely poor because early clinical diagnosis is difficult. Here, we report a case of tuberculous meningitis in a 61-year-old Indian hemodialysis patient, who presented with fever of unknown origin and was successfully treated with empiric treatment with standard four-drug regimen against tuberculosis. Comprehensive screening of the origin of fever revealed only the positive results of interferon-gamma release assay, which led us to initiate an empiric therapy for tuberculosis, before making a definitive diagnosis by cerebrospinal fluid nested PCR. Soon after the initiation of the treatment, the fever immediately abated. Although the patient experienced a single episode of paradoxical worsening and severe liver injury, she recovered well without any complications. This report provides a clinical course of the disease in a hemodialysis patient, highlighting the importance of early clinical diagnosis and rapid initiation of empirical tuberculosis treatment.
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Affiliation(s)
- Seigi Oshima
- Department of Nephrology and Dialysis, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan
| | - Minoru Sakuragi
- Department of Nephrology and Dialysis, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan
| | - Hajime Morita
- Department of Nephrology and Dialysis, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan
| | - Yuwa Oka
- Department of Neurology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan
| | - Hayato Tabu
- Department of Neurology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan
| | - Satoshi Marumo
- Department of Respiratory Disease, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan
| | - Hiroyuki Suzuki
- Department of Nephrology and Dialysis, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan
| | - Tatsuo Tsukamoto
- Department of Nephrology and Dialysis, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, 2-4-20 Ohgimachi, Kita-ku, Osaka, 530-8480, Japan.
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Luczynski P, Holmes T, Romanowski K, Arbiv OA, Cook VJ, Clark EG, Johnston JC. Risk of Tuberculosis Disease in People With Chronic Kidney Disease Without Kidney Failure: A Systematic Review and Meta-analysis. Clin Infect Dis 2023; 77:1194-1200. [PMID: 37309679 PMCID: PMC10573716 DOI: 10.1093/cid/ciad364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/24/2023] [Accepted: 06/12/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Kidney failure is an established risk factor for tuberculosis (TB), but little is known about TB risk in people with chronic kidney disease (CKD) who have not initiated kidney replacement therapy (CKD without kidney failure). Our primary objective was to estimate the pooled relative risk of TB disease in people with CKD stages 3-5 without kidney failure compared with people without CKD. Our secondary objectives were to estimate the pooled relative risk of TB disease for all stages of CKD without kidney failure (stages 1-5) and by each CKD stage. METHODS This review was prospectively registered (PROSPERO CRD42022342499). We systematically searched MEDLINE, Embase, and Cochrane databases for studies published between 1970 and 2022. We included original observational research estimating TB risk among people with CKD without kidney failure. Random-effects meta-analysis was performed to obtain the pooled relative risk. RESULTS Of the 6915 unique articles identified, data from 5 studies were included. The estimated pooled risk of TB was 57% higher in people with CKD stages 3-5 than in people without CKD (adjusted hazard ratio: 1.57; 95% CI: 1.22-2.03; I2 = 88%). When stratified by CKD stage, the pooled rate of TB was highest in stages 4-5 (incidence rate ratio: 3.63; 95% CI: 2.25-5.86; I2 = 89%). CONCLUSIONS People with CKD without kidney failure have an increased relative risk of TB. Further research and modeling are required to understand the risks, benefits, and CKD cutoffs for screening people for TB with CKD prior to kidney replacement therapy.
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Affiliation(s)
- Pauline Luczynski
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Thomas Holmes
- School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Kamila Romanowski
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Provincial TB Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Omri A Arbiv
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Victoria J Cook
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Provincial TB Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Edward G Clark
- Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - James C Johnston
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Provincial TB Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
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Sivanandam LK, Jhoond MK, Sujanyal SA, Sridhar S, Nasser N, Sanker V, Gupta U. A rare extrapulmonary manifestation of tuberculosis in a chronic kidney disease patient. Clin Case Rep 2023; 11:e7807. [PMID: 37649900 PMCID: PMC10462775 DOI: 10.1002/ccr3.7807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 07/12/2023] [Accepted: 08/04/2023] [Indexed: 09/01/2023] Open
Abstract
Key Clinical Message Chronic kidney disease (CKD) and tuberculoma are two distinct medical conditions. Nonetheless, they can be related in very rare cases. The purpose of this case report is to consider screening tests such as IGRA (interferon gamma release assay) and TST (tuberculin skin test), for tuberculosis in CKD patients with a risk of infection, thereby increasing the awareness of tuberculoma in CKD and ensuring early treatment which would eventually decrease the morbidity and mortality rates in such patients. Abstract Chronic kidney disease (CKD) associated with tuberculoma represents one of the rarest conditions occurring worldwide. Among tuberculous patients, only 1% show central nervous system involvement. We present a case of a 45-year-old male with CKD who presented with a seizure and was diagnosed to have tuberculoma.
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Affiliation(s)
| | - Manpreet Kaur Jhoond
- Team ErevnitesTrivandrumIndia
- General MedicineSri Lakshmi Narayana Institute of Medical SciencesPuducherryIndia
| | | | - Shreya Sridhar
- Team ErevnitesTrivandrumIndia
- Sapthagiri Institute of Medical Sciences and Research CentreBangaloreKarnatakaIndia
| | - Nathalie Nasser
- Team ErevnitesTrivandrumIndia
- Faculty of Medical SciencesLebanese UniversityBeirutLebanon
| | - Vivek Sanker
- Team ErevnitesTrivandrumIndia
- Noorul Islam Institute of Medical SciencesTrivandrumKeralaIndia
| | - Umang Gupta
- Team ErevnitesTrivandrumIndia
- Nepalgunj Medical CollegeNepalgunjNepal
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Kaur R, Egli T, Paynter J, Murphy R, Perumal L, Lee A, Harrison A, Christmas T, Lewis C, Nisbet M. Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment. Intern Med J 2023; 53:1588-1594. [PMID: 34936168 DOI: 10.1111/imj.15668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. AIM To characterise the population of TB-DM and TB-alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. METHODS Clinical records from all adult patients diagnosed with TB in Auckland over a 6-year period (2010-2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB-DM and TB-alone. Statistical significance was defined as P < 0.05. RESULTS A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co-existing diabetes. The TB-DM and TB-alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB-DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. CONCLUSIONS Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease.
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Affiliation(s)
- Ruveena Kaur
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
- Diabetes Centre, Auckland District Health Board, Auckland, New Zealand
| | - Tobias Egli
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
| | - Jennifer Paynter
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
| | - Rinki Murphy
- Diabetes Centre, Auckland District Health Board, Auckland, New Zealand
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Lavinia Perumal
- Auckland Regional Public Health Service (ARPHS), Auckland, New Zealand
| | - Arier Lee
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Adrian Harrison
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
| | - Tim Christmas
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
| | - Chris Lewis
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
| | - Mitzi Nisbet
- Respiratory Department, Auckland District Health Board, Auckland, New Zealand
- Infectious Diseases Department, Auckland District Health Board, Auckland, New Zealand
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10
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Alemu A, Bitew ZW, Diriba G, Seid G, Moga S, Abdella S, Gashu E, Eshetu K, Tollera G, Dangisso MH, Gumi B. The prevalence of latent tuberculosis infection in patients with chronic kidney disease: A systematic review and meta-analysis. Heliyon 2023; 9:e17181. [PMID: 37484241 PMCID: PMC10361307 DOI: 10.1016/j.heliyon.2023.e17181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 07/25/2023] Open
Abstract
Objective To estimate the prevalence of latent tuberculosis infection (LTBI) in chronic kidney disease (CKD) patients. Methods This study was conducted following the PRISMA guidelines. We identified, 3694 studies from the whole search, and 59 studies were included. Each study's quality was assessed using JBI checklist. We employed STATA version 17 for statistical analysis. We assessed heterogeneity using I2 heterogeneity test. Publication bias was assessed using funnel plot and Egger's test. We estimated the pooled LTBI prevalence in CKD patients along with 95%CI. Results The pooled prevalence of LTBI among CKD patients using data collected from 53 studies having 12,772 patients was 30.2% (95%CI; 25.5, 34.8). The pooled prevalence among pre-dialysis, hemodialysis, peritoneal dialysis, and renal transplanted patients was 17.8% (95%CI; 3.3, 32.4), 34.8% (95%CI; 29.1, 40.5), 25% (95%CI; 11, 38), and 16% (95%CI; 7, 25), respectively. The pooled prevalence of LTBI stratified by the laboratory screening methods was 25.3% (95%CI: 20.3-30.3) using TST, 28.0% (95%CI; 23.9-32.0) using QFT, and 32.6%, (95%CI: 23.7-41.5) using T-SPOT. Conclusion There is high prevalence of LTBI among CKD patients mainly in patients on dialysis. Thus, early diagnosis and treatment of LTBI in CKD patients should be performed to prevent active TB in CKD patients.PROSPERO registration number: CRD42022372441.
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Affiliation(s)
- Ayinalem Alemu
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Getu Diriba
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Getachew Seid
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Shewki Moga
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Saro Abdella
- Ethiopian Public Health Institute, Addis Ababa, Ethiopia
| | - Emebet Gashu
- Addis Ababa Health Bureau, Addis Ababa, Ethiopia
| | - Kirubel Eshetu
- USAID Eliminate TB Project, Management Sciences for Health, Addis Ababa, Ethiopia
| | | | | | - Balako Gumi
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
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Chhakchhuak M, Chaturvedy M, Agarwal J, Tak V, Bajpai NK. Retrospective Analysis of Spectrum of Infections and Antibiotic Resistance Pattern in Chronic Kidney Disease Patients on Maintenance Hemodialysis in a Tertiary Care Centre in North India. Indian J Nephrol 2023; 33:177-182. [PMID: 37448889 PMCID: PMC10337228 DOI: 10.4103/ijn.ijn_238_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/03/2021] [Accepted: 10/25/2021] [Indexed: 07/15/2023] Open
Abstract
Introduction Hemodialysis patients are at risk of infections. This study examines the spectrum of infections and antibiotic resistance patterns. Methods We retrospectively reviewed the records of 586 hemodialysis patients from May 2018 to April 2020 in a tertiary care hospital in North India. Results The study identified 99 episodes of confirmed infections. Urinary tract infections were the most common type of infections (55.5%), followed by catheter-related bloodstream infections (CRBSI) (definitive 21.2%). Other infections were pneumonia (8.1%), tuberculosis (6.1%), skin and soft tissue infection (4.0%), dengue fever (3.03%), and empyema thoracis (1.0%). Overall, Escherichia coli (33.3%) was the most common organism isolated. The most frequent uropathogens recovered were Escherichia coli (54%). In confirmed CRBSI, P. aeruginosa (23.8%) and MSSA (23.8%) were the most common pathogen isolated. K. pneumonia (37.5%) was the most common pathogen in pneumonia. Uropathogens showed the highest resistance to fluoroquinolones (93.3%-100%). Pathogens isolated in CRBSI showed maximum resistance to ciprofloxacin (100%). In pneumonia, the highest resistance was seen to third-generation cephalosporins (75%-100%). Conclusion Though the bacterial spectrum remains the same over time, antibiotic resistance is changing in uropathogens. There is a trend of predominance of Gram-negative bacterial infections in CRBSI. Tuberculosis incidence rate was much higher than the general population. There is a need for nationwide and worldwide continuous surveillance.
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Affiliation(s)
- Malsawmkima Chhakchhuak
- Department of Nephrology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Manish Chaturvedy
- Department of Nephrology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Jony Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Vibhor Tak
- Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Nitin K. Bajpai
- Department of Nephrology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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12
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Kang JY, Han K, Lee SH, Kim MK. Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up. Respir Res 2023; 24:110. [PMID: 37041513 PMCID: PMC10088122 DOI: 10.1186/s12931-023-02414-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/04/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Many have the rising coincidence of diabetes mellitus (DM) and endemic tuberculosis (TB). We evaluated whether the severity of diabetes is associated with an increased risk of active TB infection. METHODS Using a nationally representative database from the Korean National Health Insurance System, 2, 489, 718 people with type 2 DM who underwent a regular health checkup during 2009-2012 were followed up until the end of 2018. The diabetes severity score parameters included the number of oral hypoglycemic agents (≥ 3), insulin use, diabetes duration (≥ 5 years), and the presence of chronic kidney disease (CKD) or cardiovascular disease. Each of these characteristics was scored as one point, and their sum (0-5) was used as the diabetes severity score. RESULTS We identified 21, 231 cases of active TB during a median follow-up of 6.8 years. Each parameter of the diabetes severity score was associated with an increased risk of active TB (all P < 0.001). Insulin use was the most significant factor related to the risk of TB, followed by CKD. The risk of TB increased progressively with increasing diabetes severity score. After adjusting for possible confounding factors, the hazard ratio (95% confidence interval) for TB were 1.23 (1.19-1.27) in participants with one parameter, 1.39 (1.33-1.44) in those with two parameters, 1.65 (1.56-1.73) in those with three parameters, 2.05 (1.88-2.23) in those with four parameters, and 2.62 (2.10-3.27) in those with five parameters compared with participants with no parameters. CONCLUSION Diabetes severity was strongly associated in a dose-dependent manner with the occurrence of active TB. People with a higher diabetes severity score may be a targeted group for active TB screening.
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Affiliation(s)
- Ji Young Kang
- Division of Pulmonology, Department of Internal Medicine, Cheju Halla General Hospital, Jeju, 63127, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, 06978, Korea
| | - Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, #222 Banpo-daero, Seocho-Gu, Seoul, 06591, Korea.
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, #10 63-Ro, Yeongdeungpo-Gu, Seoul, 07345, Korea.
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13
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Ismail MB, Zarriaa N, Osman M, Helfawi S, Kabbara N, Chatah AN, Kamaleddine A, Alameddine R, Dabboussi F, Hamze M. Prevalence of Latent Tuberculosis Infection among Patients Undergoing Regular Hemodialysis in Disenfranchised Communities: A Multicenter Study during COVID-19 Pandemic. Medicina (B Aires) 2023; 59:medicina59040654. [PMID: 37109612 PMCID: PMC10142838 DOI: 10.3390/medicina59040654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/21/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.
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Hayuk P, Boongird S, Pornsuriyasak P, Bruminhent J. Interferon-gamma release assays for diagnosis of latent TB infection in chronic kidney diseases and dialysis patients. Front Cell Infect Microbiol 2022; 12:1046373. [PMID: 36452296 PMCID: PMC9701719 DOI: 10.3389/fcimb.2022.1046373] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/01/2022] [Indexed: 07/30/2023] Open
Abstract
Introduction Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). The prevalence and predictors of LTBI assessed by a high-sensitivity, high-specificity test such as an interferon-gamma release assay (IGRA) has not been thoroughly explored. Methods All patients with CKD were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. The prevalence of LTBI was determined using IGRA by CKD stage and dialysis type. Predictors of LTBI were assessed by logistic regression analysis. Results In total, 199 patients with CKD were enrolled (102 prospectively, 97 retrospectively). Of these, 173 patients were evaluable (mean age, 53 ± 16 years; 44% male). Ninety-five (55%) patients had ESKD and were maintained on renal replacement therapy. Overall, 39 (22.5%) patients had LTBI with a prevalence of 25.0%, 12.5%, 25.0%, 25.0%, and 24.2% among patients with CKD stage 1, 2, 3a, 3b, and ESKD, respectively (p=0.89). Among patients with ESKD, the prevalence of LTBI was higher in those on hemodialysis than in those on peritoneal dialysis (28.9% vs. 5.3%, p=0.03). In the multivariable analysis of patients with ESKD, drinking alcohol was significantly associated with LTBI (odds ratio, 8.51; 95% confidence interval, 1.24–58.38; p=0.029), and hemodialysis was marginally associated with LTBI (odds ratio, 8.14; 95% confidence interval, 0.95–69.91; p=0.056). Conclusion In TB-endemic settings, 20% of patients with CKD and 25% of patients with ESKD may have LTBI. Alcohol consumption and hemodialysis can help to identify high-risk patients with ESKD and potentially screen for LBTI.
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Affiliation(s)
- Pattorn Hayuk
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Sarinya Boongird
- Division of Nephrology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Prapaporn Pornsuriyasak
- Division of Pulmonary and Critical Care, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jackrapong Bruminhent
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Jeong YJ, Kang JY, Kim HW, Min J, Ko Y, Oh JY, Kang HH, Lim SC, Hwang HG, Shin KC, Lee HB, Kim JS, Park JS, Lee SS, Koo HK. Association of Underlying Comorbidities and Sites of tuberculosis: an analysis using surveillance data. BMC Pulm Med 2022; 22:417. [DOI: 10.1186/s12890-022-02224-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 11/04/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Background
Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site.
Methods
We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB.
Results
A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52–4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08–6.99).
Conclusions
We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.
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Sorohan BM, Ismail G, Tacu D, Obrișcă B, Ciolan G, Gîngu C, Sinescu I, Baston C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens 2022; 11:pathogens11091041. [PMID: 36145473 PMCID: PMC9505385 DOI: 10.3390/pathogens11091041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 11/18/2022] Open
Abstract
Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3–15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.
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Affiliation(s)
- Bogdan Marian Sorohan
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Correspondence: ; Tel.: +40-740156198
| | - Gener Ismail
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Dorina Tacu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Bogdan Obrișcă
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Gina Ciolan
- Department of Pneumology, Marius Nasta National Institute of Pneumology, 050159 Bucharest, Romania
| | - Costin Gîngu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
| | - Ioanel Sinescu
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
| | - Cătălin Baston
- Department of Kidney Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of General Medicine, Carol Davila University of Medicine and Pharmacy, 020022 Bucharest, Romania
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Tuberculosis incidence in patients with chronic kidney disease: a systematic review and meta-analysis. Int J Infect Dis 2022; 122:188-201. [PMID: 35609860 DOI: 10.1016/j.ijid.2022.05.046] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/04/2022] [Accepted: 05/19/2022] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE The aim of this study was to estimate global TB incidence in patients with CKD. METHODS The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was followed to perform the study. Electronic and gray literature sources were investigated for studies published between 2000 and 2021. The Joanna Briggs Institute critical appraisal checklist was used to assess the quality of the studies, and STATA version 16 was used for analysis. The I2 heterogeneity test was employed to assess heterogeneity. To examine publication bias, funnel plots and Egger's regression tests were performed. RESULTS A total of 104 studies with a sample size of 1,548,774 were included. TB incidence in patients with CKD ranges from 60 per 100,000 in the UK to 19,270 per 100,000 in China. The pooled TB incidence was estimated as 3718 per 100,000 (95%CI; 3024, 4411). Higher pooled TB incidence was found in the African region (9952/100,000, 95%CI; 6854, 13,051), followed by the South-East Asian (7200/100,000, 95%CI; 4537, 9863) and Eastern Mediterranean (5508/100,000, 95%CI; 3470, 7547) regions. In particular, patients on hemodialysis (5611/100,000) and on peritoneal dialysis (3533/100,000) had higher incidence of TB than did renal transplantation patients (2700/100,000) and patients with predialysis CKD (913/100,000). Furthermore, extrapulmonary TB (2227/100,000) was more common than pulmonary TB (1786/100,000). CONCLUSION This study identifies high TB incidence in patients with CKD with regional disparities. Thus, the authors recommend active TB screening in this group of individuals.
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Steiger S, Rossaint J, Zarbock A, Anders HJ. Secondary Immunodeficiency Related to Kidney Disease (SIDKD)-Definition, Unmet Need, and Mechanisms. J Am Soc Nephrol 2022; 33:259-278. [PMID: 34907031 PMCID: PMC8819985 DOI: 10.1681/asn.2021091257] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.
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Affiliation(s)
- Stefanie Steiger
- Division of Nephrology, Department of Medicine IV, Ludwig Maximilians University Hospital of Munich, Munich, Germany
| | - Jan Rossaint
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
| | - Alexander Zarbock
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
| | - Hans-Joachim Anders
- Division of Nephrology, Department of Medicine IV, Ludwig Maximilians University Hospital of Munich, Munich, Germany
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Thyroid tuberculosis diagnosed as papillary thyroid carcinoma with fever of unknown origin. Auris Nasus Larynx 2021; 49:1093-1097. [PMID: 34657776 DOI: 10.1016/j.anl.2021.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/06/2021] [Accepted: 09/30/2021] [Indexed: 11/20/2022]
Abstract
Thyroid tuberculosis is a rare disease, very few cases have been reported. It is difficult to diagnose because of no typical characteristics. We report on a patient who underwent surgery for suspected thyroid carcinoma, but who was then diagnosed with thyroid tuberculosis. The patient was a woman in her 70s. She had been diagnosed with chronic renal failure and had been on peritoneal dialysis. She complained of fever and a painful left anterior neck swelling. Computed tomography showed thyroid tumor with cervical lymph node swelling, ultrasound-guided fine needle aspiration cytology was suspected for papillary thyroid carcinoma. We performed surgery to confirm the diagnosis and determine treatment. Procedures for thyroid carcinoma were followed, including left lobectomy of the thyroid gland, central lymph node dissection and right cervical lymph node resection. Pathological examination found no malignant findings in the thyroid tissue but did find a granulation layer even in the right cervical lymph node. Tuberculosis-specific IFN-γ assay was positive, we diagnosed thyroid and cervical lymph node tuberculosis. Postoperatively, the neck pain and fever improved, she was treated as an outpatient with antituberculosis drugs therapy. Thyroid tuberculosis must be considered in patients with immunocompromised, such as this patient, who was on peritoneal dialysis.
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Wu CH, Su HA, Chou CA, Liu JW, Lee CT, Dai LH, Yang CC. An observational study on prevalence of latent tuberculosis infection and outcome of 3HP treatment in patients under hemodialysis in Taiwan. J Formos Med Assoc 2021; 120:1350-1360. [DOI: 10.1016/j.jfma.2020.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/03/2020] [Accepted: 10/12/2020] [Indexed: 01/20/2023] Open
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21
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Kristensen KL, Ravn P, Petersen JH, Hargreaves S, Nellums LB, Friedland JS, Andersen PH, Norredam M, Lillebaek T. Long-term risk of tuberculosis among migrants according to migrant status: a cohort study. Int J Epidemiol 2021; 49:776-785. [PMID: 32380550 DOI: 10.1093/ije/dyaa063] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2020] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The majority of tuberculosis (TB) cases in low-incidence countries occur in migrants. Only few studies have assessed the long-term TB risk in migrants after immigration, and datasets have not considered this across a range of diverse migrant groups. This nationwide study aimed to investigate long-term TB risk among migrants according to migrant status and region of origin. METHODS This cohort study included all migrants aged ≥ 18 years who obtained residence in Denmark from 1993 to 2015, with a mean follow-up of 10.8 years [standard deviation (SD) 7.3]. Migrants were categorized based on legal status of residence and region of origin. Incidence rates (IR) and rate ratios (IRR) were estimated by Poisson regression. RESULTS A total of 142 314 migrants were included. Across all migrants, the TB risk was highest during year 1 of residence (IR 275/100 000 person-years; 95% CI 249-305) followed by a gradual decline, though TB risk remained high for over a decade. Compared with the Danish-born population, the IRRs after 7-8 years were particularly higher among former asylum seekers (IRR 31; 95% CI 20-46), quota refugees (IRR 31; 95% CI 16-71), and family-reunified with refugees (IRR 22; 95% CI 12-44). Sub-Saharan African migrants also experienced elevated risk (IRR 75; 95% CI 51-109). The proportion of migrants with pulmonary TB was 52.4%. CONCLUSION All migrant groups experienced an initial high TB risk, but long-term risk remained high in key migrant groups. Most European countries focus TB screening on or soon after arrival. Our study suggests that approaches to TB screening should be adapted, with migrant populations benefiting from long-term access to preventive health services.
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Affiliation(s)
- Kristina Langholz Kristensen
- International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.,Department of Pulmonary and Infectious Diseases, Nordsjaellands Hospital, Hilleroed, Denmark
| | - Pernille Ravn
- Department of Medicine, Section of Infectious Diseases, Herlev-Gentofte Hospital, Copenhagen, Denmark
| | | | - Sally Hargreaves
- Institute for Infection & Immunity, St George's University of London, London, UK
| | - Laura B Nellums
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - Jon S Friedland
- Institute for Infection & Immunity, St George's University of London, London, UK
| | - Peter Henrik Andersen
- Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark
| | - Marie Norredam
- Research Centre for Migration, Ethnicity and Health, University of Copenhagen, Copenhagen, Denmark.,Department of Infectious Diseases, Section of Immigrant Medicine, University Hospital Hvidovre, Hvidovre, Denmark
| | - Troels Lillebaek
- International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark.,Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
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22
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Ruzangi J, Iwagami M, Smeeth L, Mangtani P, Nitsch D. The association between chronic kidney disease and tuberculosis; a comparative cohort study in England. BMC Nephrol 2020; 21:420. [PMID: 32998703 PMCID: PMC7528250 DOI: 10.1186/s12882-020-02065-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 09/15/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND People with end-stage kidney disease have an increased risk of active tuberculosis (TB). Previous systematic reviews have demonstrated that patients with chronic kidney disease (CKD) have increased risk of severe community-acquired infections. We investigated the association between CKD (prior to renal replacement therapy) and incidence of TB in UK General Practice. METHODS Using the UK Clinical Practice Research Datalink, 242,349 patients with CKD (stages 3-5) (estimated glomerular filtration rate < 60 mL/min/1.73 m2 for ≥3 months) between April 2004 and March 2014 were identified and individually matched (by age, gender, general practice and calendar time) to a control from the general population without known CKD. The association between CKD (overall and by stage) and incident TB was investigated using a Poisson regression analysis adjusted for age, gender, ethnicity, socio-economic status, chronic obstructive pulmonary disease (COPD) and diabetes. RESULTS The incidence of TB was higher amongst patients with CKD compared to those without CKD: 14.63 and 9.89 cases per 100,000 person-years. After adjusting for age, gender, ethnicity, socio-economic status, diabetes and COPD, the association between CKD and TB remained (adjusted rate ratio [RR] 1.42, 95% confidence interval [CI] 1.01-1.85). The association may be stronger amongst those from non-white ethnic minorities (adjusted RR 2.83, 95%CI 1.32-6.03, p-value for interaction with ethnicity = 0.061). Amongst those with CKD stages 3-5, there was no evidence of a trend with CKD severity. CONCLUSIONS CKD is associated with an increased risk of TB diagnosis in a UK General Practice cohort. This group of patients should be considered for testing and treating for latent TB.
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Affiliation(s)
- Judith Ruzangi
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Masao Iwagami
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
- Department of Health Services Research, Faculty of Medicine, University of Tsukuba, building #861, 1-1-1 Tenno-dai, Tsukuba, Ibaraki, Japan.
| | - Liam Smeeth
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Punam Mangtani
- Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Dorothea Nitsch
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Chiang LY, Baumann B, Romanowski K, Kumar D, Campbell JR, Djurdjev O, Morshed M, Sekirov I, Cook VJ, Levin A, Johnston JC. Latent Tuberculosis Therapy Outcomes in Dialysis Patients: A Retrospective Cohort. Am J Kidney Dis 2020; 77:696-703. [PMID: 32818551 DOI: 10.1053/j.ajkd.2020.06.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 06/20/2020] [Indexed: 11/11/2022]
Abstract
RATIONALE & OBJECTIVES Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE Systematic LTBI screening and therapy. OUTCOMES Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.
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Affiliation(s)
- Leslie Y Chiang
- British Columbia Centre for Disease Control, Vancouver, Canada; Provincial Health Services Authority, Vancouver, Canada
| | | | - Kamila Romanowski
- British Columbia Centre for Disease Control, Vancouver, Canada; Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada
| | - Divjot Kumar
- University of British Columbia, Vancouver, Canada
| | | | - Ognjenka Djurdjev
- Provincial Health Services Authority, Vancouver, Canada; British Columbia Renal, Vancouver, Canada
| | - Muhammad Morshed
- Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada; British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
| | - Inna Sekirov
- Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada; British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
| | - Victoria J Cook
- British Columbia Centre for Disease Control, Vancouver, Canada; Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada
| | - Adeera Levin
- Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada; British Columbia Renal, Vancouver, Canada
| | - James C Johnston
- British Columbia Centre for Disease Control, Vancouver, Canada; Provincial Health Services Authority, Vancouver, Canada; University of British Columbia, Vancouver, Canada.
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24
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Wu X, Liu J, Wang G, Wu F. Bone and joint tuberculosis in patients undergoing dialysis: clinical features, risk factors, and outcomes in 17 patients. J Int Med Res 2020; 48:300060520945501. [PMID: 32815456 PMCID: PMC7444120 DOI: 10.1177/0300060520945501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE This study was performed to investigate the clinical features, risk factors, and outcomes of bone and joint tuberculosis in patients undergoing dialysis. METHODS We systematically reviewed the medical records of 17 patients with bone and joint tuberculosis undergoing dialysis who were admitted to our hospital from January 2009 to January 2019. RESULTS Seventeen patients with bone and joint tuberculosis undergoing dialysis were identified in this retrospective study, and 13 patients were undergoing hemodialysis. The mean age of the 17 patients was 61.3 years (range, 32-82 years), and 10 (58.9%) patients were male. Most of the patients had a low CD4+ cell count and low hemoglobin and albumin levels. Surgery was performed in 6 patients (35.3%), and 13 of the 17 patients (76.4%) were cured. Three patients had bone or spine sequelae, mainly because of a delayed diagnosis, and one patient died of heart failure. CONCLUSION These findings indicate that older age, a low CD4+ cell count, and low hemoglobin and albumin levels are possible risk factors for bone and spine tuberculosis in patients undergoing dialysis. If diagnosed early, most patients should have a good outcome after anti-tubercular therapy with or without surgery.
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Affiliation(s)
- Xuehua Wu
- Department of Orthopedics, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, China
| | - Jing Liu
- Department of Anaesthesiology, Huzhou Maternity & Child Health Care hospital, Huzhou, Zhejiang, China
| | - Guorong Wang
- Department of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, China
| | - Fengfeng Wu
- Department of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, Zhejiang, China
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25
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Romanowski K, Rose C, Cook VJ, Sekirov I, Morshed M, Djurdjev O, Levin A, Johnston JC. Effectiveness of Latent TB Screening and Treatment in People Initiating Dialysis in British Columbia, Canada. Can J Kidney Health Dis 2020; 7:2054358120937104. [PMID: 32655871 PMCID: PMC7333484 DOI: 10.1177/2054358120937104] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 03/02/2020] [Indexed: 11/16/2022] Open
Abstract
Background: People undergoing chronic dialysis are at an increased risk of active tuberculosis (TB). In 2012, the Canadian province of British Columbia began systematically screening people initiating dialysis for latent TB using interferon-gamma release assay (IGRA), and treating when appropriate. Objective: The objective of this study was to compare active TB rate in people who initiated dialysis and were screened using an IGRA compared with those not screened during the same period. Design: Retrospective cohort study. Setting: British Columbia (BC), a Canadian province of 5.0 million people with an active TB incidence of 5.1 per 100 000 population. Participants: All people in BC who initiated at least 90 days of dialysis between January 2012 and May 2017 were included in the study. People were excluded if they were <18 years of age or had a prior history of active TB diagnosis or treatment for latent TB. Methods: A retrospective cohort was created of British Columbians who initiated dialysis between 2012 and 2017. Individuals were stratified into a screened and nonscreened group. Multivariable Cox regression was used to determine the association between latent TB screening and the development of active TB. The primary outcome was incident active TB, either microbiologically confirmed or clinically diagnosed. Results: Of the 3190 people included in the study, 1790 (56.1%) were screened, of which 152 (8.5%) initiated latent TB treatment postscreening. During follow-up, incident active TB was diagnosed in 6 (0.3%) of the 1790 people screened, compared with 11 (0.8%) of the 1400 people who received no screening. In multivariable analysis, latent TB screening and treatment was associated with a significant reduction in the rate of active TB (adjusted hazard ratio = 0.3, 95% confidence interval = 0.1-0.8; P < .01). Limitations: This was an observational retrospective study and the potential for unmeasured confounding should be carefully assessed. Conclusions: These findings suggest that systematically screening and treating people initiating dialysis can significantly decrease the rate of active TB in this high-risk population. Given the importance of screening high-risk groups, the results from this analysis could inform scale-up of TB screening in dialysis programs in other low incidence regions. Trial registration is not applicable as this was a retrospective cohort analysis and not a randomized trial.
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Affiliation(s)
- Kamila Romanowski
- British Columbia Centre for Disease Control, Vancouver, Canada.,The University of British Columbia, Vancouver, Canada
| | - Caren Rose
- British Columbia Centre for Disease Control, Vancouver, Canada.,The University of British Columbia, Vancouver, Canada
| | - Victoria J Cook
- British Columbia Centre for Disease Control, Vancouver, Canada.,The University of British Columbia, Vancouver, Canada
| | - Inna Sekirov
- The University of British Columbia, Vancouver, Canada.,British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
| | - Muhammad Morshed
- The University of British Columbia, Vancouver, Canada.,British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
| | - Ognjenka Djurdjev
- Provincial Health Services Authority, Vancouver, BC, Canada.,British Columbia Renal, Vancouver, Canada
| | - Adeera Levin
- The University of British Columbia, Vancouver, Canada.,British Columbia Renal, Vancouver, Canada
| | - James C Johnston
- British Columbia Centre for Disease Control, Vancouver, Canada.,The University of British Columbia, Vancouver, Canada
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26
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Bonkain F, De Clerck D, Dirix V, Singh M, Locht C, Mascart F, Corbière V. Early diagnosis of miliary tuberculosis in a hemodialysis patient by combining two interferon-γ-release assays: a case report. BMC Nephrol 2020; 21:214. [PMID: 32498706 PMCID: PMC7273678 DOI: 10.1186/s12882-020-01875-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 05/26/2020] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Patients with end-stage renal disease undergoing chronic hemodialysis (HD) are at high risk to develop tuberculosis (TB) associated with a high mortality rate. TB diagnosis is often delayed due to non-specific symptoms, frequent extra-pulmonary manifestations, and rare microbiological confirmation. This case report illustrates the clear added value of combined interferon-γ -release assays (IGRA) in response to different mycobacterial antigens for an early diagnosis of TB in HD patients. CASE PRESENTATION We report the case of an Egyptian patient under chronic HD treatment, who presented with recurrent episodes of fever and myalgia of unknown origin, associated with an important inflammatory syndrome. These episodes resolved partially or completely within less than 1 month without any treatment but recurred 10 times within 3 years. Chest Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18FDG PET-CT) demonstrated several active mediastinal lymphadenopathies. TB was the first suspected diagnosis but cultures and polymerase chain reaction (PCR) remained negative on a mediastinal lymph node aspiration. In contrast, the results from two different IGRA performed on blood were highly suggestive of TB disease. Several granulomas, some of them with central non-caseating necrosis, were demonstrated on a pulmonary nodule obtained by thoracoscopic resection, but PCR and culture remained negative for M. tuberculosis. Three years after the initial symptoms, a new PET-CT revealed a retro-clavicular lymphadenopathy in addition to the mediastinal lymphadenopathies, and the M. tuberculosis culture performed on the resected lymphadenopathy was positive. Antibiotic treatment for TB was started and resulted in a clear improvement of the patient's clinical condition, allowing him to successfully receive a renal graft. CONCLUSIONS In view of the high frequency of TB in patients undergoing chronic HD and of the limitations of the classical diagnosis procedures, nephrologists have to diagnose TB mostly on clinical suspicion. We demonstrate here that the use of a combined IGRA to two different mycobacterial antigens may significantly raise the index of suspicion and help clinicians to decide starting anti-TB treatment in HD patients.
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Affiliation(s)
- Florence Bonkain
- Department of Nephrology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
| | - Dieter De Clerck
- Department of Nephrology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
| | - Violette Dirix
- Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium
| | - Mahavir Singh
- Lionex Diagnostics and Therapeutics, Braunschweig, Germany
| | - Camille Locht
- U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, F-59000, Lille, France
| | - Françoise Mascart
- Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
| | - Véronique Corbière
- Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium
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27
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Zhang J, Zhang J, Sun M, Zhou Q, Liu Y, Chen C, You X. Tuberculosis spondylitis in patients on hemodialysis: Clinical features, risk factors, and outcomes in 12 patients. Ther Apher Dial 2020; 25:50-54. [PMID: 32314489 DOI: 10.1111/1744-9987.13505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 04/08/2020] [Accepted: 04/16/2020] [Indexed: 11/29/2022]
Abstract
The aim of this study was to investigate the clinical features, risk factors and outcomes of tuberculosis spondylitis (TBS) in patients on hemodialysis (HD). We systematically reviewed medical records from 12 HD patients with TBS admitted to our hospital from April 2008 to April 2018. A total of 120 age- and sex-matched HD patients without infections were randomly selected as controls. The incidence of TBS in our patient group was 1.5/1000 per year. The average duration from initial symptoms to diagnosis was 45.4 days (range, 11-180 days). Neurosurgery was performed in 4 (33.3%) patients. TBS was cured or improved in 11 (91.7%) patients. HD patients with TBS had significantly lower albumin and Hb levels than controls (P = .03 and P = .01). These findings indicated that lower albumin and Hb levels were possible risk factors for TBS in patients on HD, most HD patients with TBS had a good outcome after anti-TB therapy with or without surgery.
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Affiliation(s)
- Jianna Zhang
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ji Zhang
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mei Sun
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qiongxiu Zhou
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yi Liu
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chaosheng Chen
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaohan You
- Department of Nephrology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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28
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Ganz T, Aronoff GR, Gaillard CAJM, Goodnough LT, Macdougall IC, Mayer G, Porto G, Winkelmayer WC, Wish JB. Iron Administration, Infection, and Anemia Management in CKD: Untangling the Effects of Intravenous Iron Therapy on Immunity and Infection Risk. Kidney Med 2020; 2:341-353. [PMID: 32734254 PMCID: PMC7380433 DOI: 10.1016/j.xkme.2020.01.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Patients with chronic kidney disease (CKD) are at increased risk for infection, attributable to immune dysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non-transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study.
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Affiliation(s)
- Tomas Ganz
- Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA
| | | | | | - Lawrence T Goodnough
- Department of Pathology, Stanford University, Stanford, CA.,Department of Medicine (Hematology), Stanford University, Stanford, CA
| | - Iain C Macdougall
- Department of Renal Medicine, King's College Hospital, London, United Kingdom
| | - Gert Mayer
- Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria
| | - Graça Porto
- Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.,i3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
| | - Wolfgang C Winkelmayer
- Section of Nephrology and Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, TX
| | - Jay B Wish
- Division of Nephrology, Indiana University Health, Indianapolis, IN
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29
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Sookaromdee P, Wiwanitkit V. Expected tuberculosis detection rate among the patients with chronic kidney disease: A report from endemic country of tuberculosis. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2020; 31:701-702. [DOI: 10.4103/1319-2442.289461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
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30
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Mamishi S, Pourakbari B, Moradzadeh M, van Leeuwen WB, Mahmoudi S. Prevalence of active tuberculosis infection in transplant recipients: A systematic review and meta-analysis. Microb Pathog 2019; 139:103894. [PMID: 31805320 DOI: 10.1016/j.micpath.2019.103894] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 11/24/2019] [Accepted: 11/25/2019] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Tuberculosis (TB) is considered as a serious complication of organ transplant; therefore, the detection and appropriate treatment of active TB infection is highly recommended for the reduction of mortality in the future. The aim of this review was to conduct a systematic review and meta-analysis assessing the prevalence of active TB infection in transplant recipients (TRs). MATERIAL AND METHODS Electronic databases, including MEDLINE (via PubMed), SCOPUS and Web of Science were searched up to December 24, 2017. The prevalence of active TB was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 14. RESULTS The pooled prevalence of post-transplant active TB was estimated 3% [95% CI: 2-3]. The pooled prevalence of active TB in different transplant forms was as follows: renal,3% [95% CI: 2-4]; stem cell transplant (SCT), 1% [95% CI: 0-3]; lung, 4% [95% CI: 2-6]; heart, 3% [95% CI: 2-4]; liver, 1% [95% CI: 1], and hematopoietic stem cell transplant (HSCT), 2% [95% CI: 1-3]. The prevalence of different clinical presentations of TB was as follows: pulmonary TB (59%; 95% CI: 54-65), extra pulmonary TB (27%; 95% CI: 21-33), disseminated TB (15%; 95% CI: 12-19) and miliary TB (8%; 95% CI: 4-13). The pooled prevalence of different diagnostic tests was as follows: chest X-ray, 57% [95% CI, 46-67]; culture, 56% [95% CI, 45-68]; smear, 49% [95% CI, 40-58]; PCR, 43% [95% CI, 40-58]; histology, 26% [95% CI, 20-32], and tuberculin skin test, 19% [95% CI, 10-28]. CONCLUSION A high suspicion level for TB, the early diagnosis and the prompt initiation of therapy could increase the survival rates among SOT patients. Overall, renal and lung TRs appear to have a higher predisposition for acquiring TB than other type of recipients. Monitoring of the high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection among TRs especially in endemic areas.
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Affiliation(s)
- Setareh Mamishi
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran; Department of Infectious Diseases, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Pourakbari
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Mina Moradzadeh
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Willem B van Leeuwen
- Department of Innovative Molecular Diagnostics, University of Applied Sciences Leiden, Leiden, the Netherlands
| | - Shima Mahmoudi
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran.
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31
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Lee MC, Lee CH, Lee MR, Wang JY, Chen SM. Impact of metformin use among tuberculosis close contacts with diabetes mellitus in a nationwide cohort study. BMC Infect Dis 2019; 19:936. [PMID: 31694558 PMCID: PMC6836500 DOI: 10.1186/s12879-019-4577-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 10/18/2019] [Indexed: 10/28/2022] Open
Abstract
BACKGROUND The protective effect of metformin against active tuberculosis (TB) among TB close contacts is unknown. METHODS TB close contacts with diabetes mellitus (DM) and normal renal function were selected from the National Health Insurance Research Database of Taiwan. Metformin users were patients who received ≥90 cumulative defined daily doses within 1 year before the index date. For each metformin user, a propensity-score matched metformin nonuser and an age- and sex-matched healthy TB close contact were selected. The outcome was incident TB, identified using previously validated diagnostic criteria. Independent predictors were investigated using stratified Cox regression analysis. Interaction analysis was also performed. RESULTS A total of 5846 TB close contacts who were metformin users, metformin non-users, and healthy contacts were analysed. The incidence of active TB was 755 (600-938), 1117 (927-1335), and 526 (393-689) cases per 100,000 person-years in each group, respectively. Multivariate analysis revealed that healthy contacts had the lowest risk of developing active TB (adjusted hazard ratio [aHR]: 0.42 [0.30-0.60]) and metformin use partially reversed the risk associated with DM (aHR: 0.73 [0.54-0.98]). Subpopulation analysis revealed a significant interaction between insulin use and metformin use. CONCLUSIONS Metformin use is associated with a lower risk of developing active TB among TB close contacts with DM, especially for insulin users. It may be an alternative choice for primary prevention against active TB if no contraindications exist. However, prospective studies are needed to confirm the findings.
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Affiliation(s)
- Ming-Chia Lee
- Department of Pharmacy, New Taipei City Hospital, #3, Sec. 1, New Taipei Blvd., Sanchong Dist, New Taipei City, 24141, Taiwan.,School of Pharmacy, College of Pharmacy, Taipei Medical University, #250, Wuxing St, Taipei, 11031, Taiwan
| | - Chih-Hsin Lee
- Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, #111, Sec. 3, Xinglong Rd., Wenshan Dist, Taipei, 11696, Taiwan.,Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, #250, Wuxing St, Taipei, 11031, Taiwan
| | - Meng-Rui Lee
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu, Branch, #25,Lane 442,Sec.1,Jingguo Rd., Hsin-chu, 300, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, #7, Chung-Shan South Road, Taipei, 10002, Taiwan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, #17, Xuzhou Rd., Zhongzheng Dist, Taipei, 10055, Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, #7, Chung-Shan South Road, Taipei, 10002, Taiwan.
| | - Shih-Ming Chen
- School of Pharmacy, College of Pharmacy, Taipei Medical University, #250, Wuxing St, Taipei, 11031, Taiwan.
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32
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Park S, Lee S, Kim Y, Lee Y, Kang MW, Cho S, Han K, Han SS, Lee H, Lee JP, Joo KW, Lim CS, Kim YS, Kim DK. Association of CKD with Incident Tuberculosis. Clin J Am Soc Nephrol 2019; 14:1002-1010. [PMID: 31171591 PMCID: PMC6625615 DOI: 10.2215/cjn.14471218] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 05/06/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES The incidence and risk of Mycobacterium tuberculosis in people with predialysis CKD has rarely been studied, although CKD prevalence is increasing in certain countries where Mycobacterium tuberculosis is endemic. We aimed to investigate the association between predialysis CKD and active Mycobacterium tuberculosis risks in a nation with moderate Mycobacterium tuberculosis risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this nationwide retrospective cohort study, we reviewed the National Health Insurance Database of Korea, screening 17,020,339 people who received a national health screening two or more times from 2012 to 2016. Predialysis CKD was identified with consecutive laboratory results indicative of CKD (e.g., persistent eGFR <60 ml/min per 1.73 m2 or dipstick albuminuria). People with preexisting active Mycobacterium tuberculosis or kidney replacement therapy were excluded. A 1:1 matched control group without CKD was included with matching for age, sex, low-income status, and smoking history. The risk of incident active Mycobacterium tuberculosis, identified in the claims database, was assessed by the multivariable Cox regression model, which included both matched and unmatched variables (e.g., body mass index, diabetes, hypertension, places of residence, and other comorbidities). RESULTS We included 408,873 people with predialysis CKD and the same number of controls. We identified 1704 patients with active Mycobacterium tuberculosis (incidence rate =137.5/100,000 person-years) in the predialysis CKD group and 1518 patients with active Mycobacterium tuberculosis (incidence rate =121.9/100,000 person-years) in the matched controls. The active Mycobacterium tuberculosis risk was significantly higher in the predialysis CKD group (adjusted hazard ratio, 1.21; 95% confidence interval, 1.13 to 1.30). The risk factors for active Mycobacterium tuberculosis among the predialysis CKD group were old age, men, current smoking, low income, underlying diabetes, chronic obstructive pulmonary disease, and Kidney Disease Improving Global Outcomes CKD stage 1 (eGFR≥90 ml/min per 1.73 m2 with persistent albuminuria) or stage 4/5 without dialysis (eGFR<30 ml/min per 1.73 m2). CONCLUSIONS In the Korean population, the incidence of active Mycobacterium tuberculosis was higher in people with versus without predialysis CKD.
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Affiliation(s)
- Sehoon Park
- Departments of Biomedical Sciences and.,Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Soojin Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Internal Medicine and
| | - Yaerim Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Keimyung University School of Medicine
| | - Yeonhee Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Internal Medicine and
| | - Min Woo Kang
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Internal Medicine and
| | - Semin Cho
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kyungdo Han
- Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, Korea; and
| | - Seoung Seok Han
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Pyo Lee
- Internal Medicine and.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Internal Medicine and.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Chun Soo Lim
- Internal Medicine and.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yon Su Kim
- Departments of Biomedical Sciences and.,Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Internal Medicine and.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; .,Internal Medicine and.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Impact of renal function-based anti-tuberculosis drug dosage adjustment on efficacy and safety outcomes in pulmonary tuberculosis complicated with chronic kidney disease. BMC Infect Dis 2019; 19:374. [PMID: 31046706 PMCID: PMC6498605 DOI: 10.1186/s12879-019-4010-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 04/22/2019] [Indexed: 11/22/2022] Open
Abstract
Background Dosages of anti-tuberculosis (TB) drugs are recommended to be adjusted according to renal function for patients complicated with chronic kidney disease (CKD). However, the efficacy and safety outcomes of such renal function-based dosage adjustments are not fully elucidated. Methods We retrospectively reviewed cases of pulmonary TB susceptible to first-line drugs that were treated at Jikei University Daisan Hospital between 2005 and 2014 with standard regimens based on dosage adjustments according to renal function recommended by international guidelines. Patients were divided into four groups, those with no, mild, moderate or severe CKD. In-hospital TB-related mortality, the rate of sputum culture conversion at 2 months, the frequency of adverse events (AEs), for which at least the temporal discontinuation of the suspect drug was required for patient improvement, and the rate of regimen change due to AEs were assessed. Results In the 241 enrolled patients (mean age, 64.1 years; 143 men), fourteen patients (5.8%) died due to TB during their hospitalization. The rate of sputum culture conversion at 2 months was 78.0%. The frequency of in-hospital TB-related death and the conversion rate in the groups did not vary significantly according to CKD severity including those in the non-CKD group (P = 0.310 and P = 0.864). Meanwhile, a total of 70 AEs were observed in 60 patients (24.9%) and the difference between the groups in the overall frequency of AEs was almost significant (P = 0.051). Moreover, for the 154 patients with CKD, severe CKD stage was a significant risk factor for regimen change (OR = 5.92, 95% CI = 1.08–32.5, P = 0.041), as were drug-induced hepatitis and cutaneous reaction (OR = 35.6, 95% CI = 8.70–145, P < 0.001; OR = 17.4, 95% CI = 3.16–95.5, P = 0.001; respectively). Conclusions Adjusting the dosage of TB treatment for CKD patients according to the guidelines was efficient in terms of similar therapeutic outcome to that of the non-CKD group. However, AEs warrant attention to avoid regimen change in patients with severe CKD, even if the renal function-based dosage adjustment is performed. Electronic supplementary material The online version of this article (10.1186/s12879-019-4010-7) contains supplementary material, which is available to authorized users.
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Wang H, Wang S, Xu L, Mao Y. The Application of T.SPOT-TB Assay for Early Diagnosis of Active Tuberculosis in Chronic Kidney Disease Patients Receiving Immunosuppressive Treatment. J INVEST SURG 2019; 33:853-858. [PMID: 30917713 DOI: 10.1080/08941939.2019.1566417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: The current study investigated the clinical application of the T-SPOT.TB assay for detecting tuberculosis (TB) infection in chronic kidney disease patients treated with immunosuppressive therapy. Methods: Clinical data from 91 patients were retrospectively analyzed. The rate of positive T-SPOT.TB results and spot numbers were compared before and after treatment. Clinical characteristics that may affect the test results were also investigated. Results: Two active TB cases were observed after immunosuppressive treatment, and eight patients with negative T-SPOT.TB results at baseline had positive results after treatment. No significant changes in spot numbers were observed for patients who were positive at baseline. Compared with pretreatment baseline, patients who received medium/high doses of corticosteroids had a greater number of T-SPOT.TB positive results (p = 0.016) and CFP-10 spots (p = 0.041) after treatment. For patients who received combination therapy with medium/high doses of corticosteroids, the T-SPOT.TB positive rate (p = 0.046) and CFP-10 spot number (p = 0.041) were increased after treatment, with no significant changes in the total number of spots or ESAT-6 spots. For those who received combination therapy with low doses of corticosteroids and those who received single immunosuppressive medication, there were no significant differences in the T-SPOT.TB positive rate, total spot number, or numbers of ESAT-6 and CFP-10 spots. Conclusion: The increase in positive T-SPOT.TB results was mainly associated with medium/high doses of glucocorticoids. The active TB cases might represent new infections. Regular monitoring using the T-SPOT.TB assay will help in the early detection of active TB.
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Affiliation(s)
- Haitao Wang
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Songlan Wang
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Lengnan Xu
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Yonghui Mao
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Beijing, China
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35
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Connolly R, Denton MD, Humphreys H, McLoughlin RM. Would hemodialysis patients benefit from a Staphylococcus aureus vaccine? Kidney Int 2019; 95:518-525. [PMID: 30691691 DOI: 10.1016/j.kint.2018.10.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/17/2018] [Accepted: 10/05/2018] [Indexed: 11/19/2022]
Abstract
Staphylococcus aureus bloodstream infection can have potentially catastrophic consequences for patients on hemodialysis. Consequently, an effective vaccine to prevent S aureus infection would have a significant influence on morbidity and mortality in this group. To date, however, efforts to develop a vaccine have been unsuccessful. Previous antibody-inducing vaccine candidates did not prevent or attenuate S aureus infection in clinical trials. Recent advances have helped to elucidate the role of specific T-cell subsets, notably T-helper cell 1 and T-helper cell 17, in the immune response to S aureus. These cells are essential for coordinating an effective phagocytic response via cytokine production, indirectly leading to destruction of the organism. It is now widely accepted that next-generation S aureus vaccines must also induce effective T-cell-mediated immunity. However, there remains a gap in our knowledge: how will an S aureus vaccine drive these responses in those patients most at risk? Given that patients on hemodialysis are an immunocompromised population, in particular with specific T-cell defects, including defects in T-helper cell subsets, this is likely to affect their ability to respond to an S aureus vaccine. We urgently need a better understanding of T-cell-mediated immunity in this cohort if an efficacious vaccine is ever to be realized for these patients.
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Affiliation(s)
- Roisin Connolly
- Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Dublin, Ireland; Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Microbiology, Beaumont Hospital, Dublin, Ireland
| | - Mark D Denton
- Beaumont Kidney Centre, Beaumont Hospital, Dublin, Ireland
| | - Hilary Humphreys
- Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Microbiology, Beaumont Hospital, Dublin, Ireland
| | - Rachel M McLoughlin
- Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Dublin, Ireland.
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36
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Min J, Kwon SK, Jeong HW, Han JH, Kim YJ, Kang M, Kang G. End-stage Renal Disease and Risk of Active Tuberculosis: a Nationwide Population-Based Cohort Study. J Korean Med Sci 2018; 33:e341. [PMID: 30595682 PMCID: PMC6306323 DOI: 10.3346/jkms.2018.33.e341] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 10/09/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The converging epidemics of tuberculosis (TB) and end-stage renal disease (ESRD) have generated a significant public health burden, however, previous studies have been limited to a small number of patients. This nationwide cohort study aimed to assess the rate of developing active TB among patients receiving dialysis for ESRD. METHODS The Korean national health insurance database was used to identify patients receiving dialysis for new-onset ESRD during 2004-2013, who were propensity score matched to an equivalent number of non-dialysis subjects from the general population. The incidences of active TB in the ESRD and control cohorts were calculated for 2004-2013, and multivariable Cox proportional hazards model was used to evaluate the ESRD-related risk of active TB. RESULTS During 2004-2013, 59,584 patients received dialysis for newly diagnosed ESRD. In the dialysis and control cohorts, 457 (0.8%) and 125 (0.2%) cases of active TB were detected, respectively. Patients with ESRD were associated with a significantly higher risk of active TB compared to the controls (incidence rate ratio, 4.80). The ESRD cohort had an independently elevated risk of active TB (adjusted hazard ratio, 4.39; 95% confidence interval, 3.60-5.37). CONCLUSION We found that patients receiving dialysis for ESRD had an elevated risk of active TB. These results highlight the need for detailed and well-organised guidelines for active TB screening among patients with ESRD.
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Affiliation(s)
- Jinsoo Min
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Soon Kil Kwon
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Hye Won Jeong
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Joung-Ho Han
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Yeonkook Joseph Kim
- Graduate School of Health Science Business Convergence, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Minseok Kang
- Department of Health Information and Management, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Gilwon Kang
- Department of Health Information and Management, Chungbuk National University College of Medicine, Cheongju, Korea
- Chungbuk Regional Cardiovascular Center, Chungbuk National University Hospital, Cheongju, Korea
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Lee MC, Chiang CY, Lee CH, Ho CM, Chang CH, Wang JY, Chen SM. Metformin use is associated with a low risk of tuberculosis among newly diagnosed diabetes mellitus patients with normal renal function: A nationwide cohort study with validated diagnostic criteria. PLoS One 2018; 13:e0205807. [PMID: 30335800 PMCID: PMC6193668 DOI: 10.1371/journal.pone.0205807] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 10/02/2018] [Indexed: 12/22/2022] Open
Abstract
Human studies on the use of metformin as host-directed therapy (HDT) for tuberculosis (TB) are rare. We performed a nationwide cohort study to evaluate the effect of metformin on mitigating the risk of active TB among patients with diabetes mellitus (DM). Among newly diagnosed DM patients identified in the Taiwan National Health Insurance Research Database, metformin users, defined on the basis of >90 cumulative defined daily doses within 1 year, and propensity-score-matched metformin nonusers were selected. The primary outcome was incident TB, identified using diagnostic criteria validated by real patient data at a medical center. Independent predictors were investigated using Cox regression analysis. Similar analysis was performed in a subpopulation without a history of hypertensive nephropathy and renal replacement therapy. A total of 88,866 metformin users and 88,866 propensity-score-matched nonusers were selected. Validation results showed that the TB diagnostic criteria had a sensitivity of 99.13% and specificity of 99.90%. During follow-up, 707 metformin users and 807 nonusers developed active TB. Metformin use was independently associated with a lower risk of incident TB (hazard ratio [HR]: 0.84 [0.74-0.96]). TB risk was lower in high-dose metformin users than in low-dose users (HR: 0.83 [0.72-0.97]). The effect of metformin remained when analysis was restricted in the subpopulation without renal function impairment. Newly diagnosed diabetic patients without contraindication should receive metformin as an anti-diabetic medication, with potential additional benefit against TB.
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Affiliation(s)
- Ming-Chia Lee
- Department of Pharmacy, New Taipei City Hospital, New Taipei City, Taiwan
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Chen-Yuan Chiang
- Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- International Union Against Tubercle and Lung Disease, Paris, France
| | - Chih-Hsin Lee
- Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hao Chang
- Department of Internal Medicine, National Taiwan University Hospital, Hsinchu branch, Hsinchu, Taiwan
| | - Jann-Yuan Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Ming Chen
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
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Vikrant S. Tuberculosis in dialysis: Clinical spectrum and outcome from an endemic region. Hemodial Int 2018; 23:88-92. [PMID: 30289617 DOI: 10.1111/hdi.12693] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 08/05/2018] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Tuberculosis (TB) is a significant health problem in developing countries. There are limited data on TB among end stage renal disease (ESRD) patients on maintenance dialysis in India. Clinical profile and outcome of TB in dialysis were studied. METHODS Retrospective study of ESRD patients who were on maintenance dialysis (either peritoneal dialysis [PD] or hemodialysis (HD]) and diagnosed to have TB over a period of 11 years. FINDINGS Thirty-two patients had a diagnosis of TB. Mean age of the patients was 50.3 ±13.9 years. The majority (56.2%) of the patients were female. The modality of dialysis was HD in 53.1% and PD in 46.9%. Mean duration of dialysis at the diagnosis of TB was 15.1 ± 13.9 months. Over three-quarter of the patients had an extrapulmonary involvement. Pleuro-pulmonary (40.6%), peritoneum (34.4%), and lymph node (15.6%) were the most common sites for TB. About 6.3%patients had disseminated TB, and 3.1% had pericardial TB. The clinical presentation of TB was: fever/pyrexia of unknown origin 28.1%, constitutional symptoms of anorexia, fever, night sweats and weight loss 34.4%, abnormal chest radiograph 37.5%, ascites/peritonitis 34.4%, pleural effusion 25%, lymphadenopathy 18.8%, meningoencephalitis 6.3%, and pericardial effusion 3.1%. Peritoneal TB presented as nonresolving peritonitis in PD and ascites in HD. The diagnosis was a microbiological/histological in 50% and rest 50% only on clinical grounds. Nine (29%) patients had adverse effects of anti-TB drugs. Four patients of TB peritonitis had a poor gastrointestinal tolerance of anti-TB drugs and defaulted on the treatment and had an adverse outcome. About 53.1% of the patients survived, and 46.9% died. DISCUSSION TB in dialysis is mostly extrapulmonary. Early diagnosis is difficult, and the adverse effects of anti-TB medications complicate the treatment. TB in dialysis carries high morbidity and mortality. TB peritonitis has a poor prognosis.
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Affiliation(s)
- Sanjay Vikrant
- Department of Nephrology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
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Deniz S, Aydemir Y, Şengül A, Emre JÇ, Tanrisev M, Özhan MH, Güney İ. Factors affecting TST level in patients undergoing dialysis: a multicenter study. Hemodial Int 2018; 23:81-87. [PMID: 30289192 DOI: 10.1111/hdi.12676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 04/30/2018] [Indexed: 02/01/2023]
Abstract
INTRODUCTION The risk of TB is increased in patients with chronic kidney disease (CKD) when compared with individuals with normal renal function. We aimed to determine tuberculin skin test (TST) response and the factors which might affect the response in patients with CKD undergoing dialysis in this study. METHODS The purified protein derivative solution was administered to the patients and the diameter of induration was measured. Additionally, the age, gender and smoking status of the patients were interrogated. Comorbidities were recorded both by patients' self-reports and data from the hospital files. The number of Bacille Calmette-Guerin (BCG) scars was recorded by checking both shoulders. FINDINGS The study was conducted with a total of 371 patients (194 men and 177 women). The mean age was 60.09 ± 15.88, TST was 6.99 ± 6.9, duration of dialysis was 4.44 ± 4.5 (3.8-0.1,24). A total of 229 patients have comorbodities (61.7%, the most frequent was hypertension). Logistic regression model was performed. Gender, vitamin D treatment and high parathormone (PTH) levels remained in the final stage of the analysis and vitamin D intake and PTH levels were detected to be statistically significant (P = 0.002, 0.007, respectively). DISCUSSION This study is the first study which showed a correlation between TST negativity and increased PTH levels and receiving vitamin D treatment. Starting from this point, it was concluded that PTH may suppress the immune system and especially cellular immunity.
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Affiliation(s)
- Sami Deniz
- Clinic of Chest Diseases Dr. Suat Seren Chest Diseases and Thoracic Surgery Research and Education Hospital, İzmir, Turkey
| | - Yusuf Aydemir
- Chest Diseases Department, Sakarya University, Sakarya, Turkey
| | - Aysun Şengül
- Kocaeli Derince Research and Education Hospital, Derince, Kocaeli, Turkey
| | | | - Mehmet Tanrisev
- Department of Nephrology, Tepecik Research and Education Hospital, İzmir, Turkey
| | | | - İbrahim Güney
- Nephrology Department, Konya Research and Training Hospital, Konya, Turkey
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Epidemiology, detection, and management of tuberculosis among end-stage renal disease patients. Infect Control Hosp Epidemiol 2018; 39:1367-1374. [PMID: 30231948 DOI: 10.1017/ice.2018.219] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Tuberculosis (TB) remains an important problem among end-stage renal disease (ESRD) patients. We reviewed the epidemiology of TB and ESRD, investigations of TB exposures in US dialysis facilities, and published guidelines to inform screening and treatment practices among US ESRD patients. Compared to TB in the general population, ESRD patients have 6-25-fold higher TB incidence rates, and mortality during treatment is 2-3-fold higher. Most TB cases among ESRD patients (~90%) occur among non-US-born persons, and an analysis of genotyping data suggests that 80% of all cases result from latent TB infection (LTBI) reactivation. Published TB contact investigations in dialysis facilities have reported cases among ESRD patients and healthcare workers. However, transmission of TB is rare: there were no reports of secondary cases of TB because of exposure to an index-case patient and there were few TB infections, which was demonstrated by low occurrence of newly positive tuberculin skin tests (12%-16%) and conversions (8%-17%) among contacts. Targeted TB education, screening, and treatment for ESRD patients at highest risk for TB exposure (eg, non-US-born persons), using interferon-gamma release assays and short course LTBI regimens (ie, isoniazid-rifapentine weekly for 12 weeks or rifampin daily for 4 months) may be an effective overall strategy for reducing TB burden in ESRD patients.
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Cheng KC, Liao KF, Lin CL, Liu CS, Lai SW. Chronic kidney disease correlates with increased risk of pulmonary tuberculosis before initiating renal replacement therapy: A cohort study in Taiwan. Medicine (Baltimore) 2018; 97:e12550. [PMID: 30278552 PMCID: PMC6181567 DOI: 10.1097/md.0000000000012550] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
This study aimed to assess the association between chronic kidney disease (CKD) and the risk of pulmonary tuberculosis (TB) before initiating renal replacement therapy (RRT) in Taiwan.Total 16,052 subjects newly diagnosed with CKD between 2000 and 2012 were included in the CKD group, and 31,949 randomly selected subjects who did not have CKD formed the non-CKD group. Subjects with a history of pulmonary TB or RRT, including dialysis and renal transplantation, before the index date were excluded. We determined the incidence of pulmonary TB at the end of 2013. A multivariable Cox proportional hazards regression model was used to assess the hazard ratio (HR) and 95% confidence interval (CI) for the risk of developing pulmonary TB associated with CKD.The overall incidence of pulmonary TB was 1.47-fold greater in the CKD group compared to that in the non-CKD group (4.94 vs 3.35 per 1000 person-years, 95% CI 1.39, 1.56). Multivariable Cox proportional hazards regression analysis showed that the adjusted HR of pulmonary TB was 1.45-fold higher in the CKD group (95% CI 1.27, 1.64) than in the non-CKD group. Male sex (adjusted HR 2.04), age (increase per one year, adjusted HR 1.05), chronic obstructive pulmonary disease (adjusted HR 1.54), and diabetes mellitus (adjusted HR 1.34) were also associated with pulmonary TB.CKD is associated with an increased risk of developing pulmonary TB before the initiation of RRT.
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Affiliation(s)
- Kao-Chi Cheng
- College of Medicine, China Medical University
- Department of Family Medicine, China Medical University Hospital
- Department of Food and Nutrition, Providence University
| | - Kuan-Fu Liao
- Division of Hepatogastroenterology, Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung
- College of Medicine, Tzu Chi University, Hualien
| | - Cheng-Li Lin
- College of Medicine, China Medical University
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Chiu-Shong Liu
- College of Medicine, China Medical University
- Department of Family Medicine, China Medical University Hospital
| | - Shih-Wei Lai
- College of Medicine, China Medical University
- Department of Family Medicine, China Medical University Hospital
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Moran E, Baharani J, Dedicoat M, Robinson E, Smith G, Bhomra P, Thien OS, Ryan R. Risk factors associated with the development of active tuberculosis among patients with advanced chronic kidney disease. J Infect 2018; 77:291-295. [PMID: 29928915 DOI: 10.1016/j.jinf.2018.06.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 04/04/2018] [Accepted: 06/04/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVES The risk of developing active TB is greater in those receiving haemodialysis. This study aimed to describe the incidence of active tuberculosis among patients referred for management of kidney disease and dialysis in a high incidence UK city, with the purpose of informing latent TB testing and treatment practice. METHODS Information from the tuberculosis register was cross-referenced with the Department of Renal Medicine patient information system. All patients seen between 1st January 2005 and 1st October 2016 were included in the analyses with the exception of those with prior TB. RESULTS 68 cases of active TB were identified, an incidence of 126/100,000 patient-years (95% CI 97-169). Incidence was lowest in those with CKD 1 or 2 and rose as high as 256/100,000 patient-years (95% CI 183-374) in those receiving renal replacement therapy. 48% of cases were pulmonary and 87% of TB patients gave their ethnicity as either black/black British or Asian/Asian British, significantly more than in the non-TB renal group. Cases occurred steadily over the time period in which patients were in the cohort. CONCLUSION TB incidence was very high among those receiving renal replacement therapy or CKD 4 or 5. Most cases occurred in those of an Asian/Asian British or black/black British background. Testing and treating such patients for latent TB is justified and should include those who have been receiving renal replacement therapy for some years.
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Affiliation(s)
- E Moran
- Dept of Infection, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
| | - J Baharani
- Dept of Renal Medicine, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M Dedicoat
- Dept of Infection, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - E Robinson
- Public Health England, Heartlands Hospital, UK
| | - G Smith
- Public Health England, Heartlands Hospital, UK
| | - P Bhomra
- Dept of Infection, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - O S Thien
- Dept of Infection, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - R Ryan
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK; Medical Innovation, Research and Development Unit, University Hospitals Birmingham Foundation Trust, Birmingham, UK
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Qian X, Nguyen DT, Lyu J, Albers AE, Bi X, Graviss EA. Risk factors for extrapulmonary dissemination of tuberculosis and associated mortality during treatment for extrapulmonary tuberculosis. Emerg Microbes Infect 2018; 7:102. [PMID: 29872046 PMCID: PMC5988830 DOI: 10.1038/s41426-018-0106-1] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/15/2018] [Accepted: 04/29/2018] [Indexed: 01/28/2023]
Abstract
Many environmental, host, and microbial characteristics have been recognized as risk factors for dissemination of extrapulmonary tuberculosis (EPTB). However, there are few population-based studies investigating the association between the primary sites of tuberculosis (TB) infection and mortality during TB treatment. De-identified population-based surveillance data of confirmed TB patients reported from 2009 to 2015 in Texas, USA, were analyzed. Regression analyses were used to determine the risk factors for EPTB, as well as its subsite distribution and mortality. We analyzed 7007 patients with exclusively pulmonary TB, 1259 patients with exclusively EPTB, and 894 EPTB patients with reported concomitant pulmonary involvement. Age ≥45 years, female gender, human immunodeficiency virus (HIV)-positive status, and end-stage renal disease (ESRD) were associated with EPTB. ESRD was associated with the most clinical presentations of EPTB other than meningeal and genitourinary TB. Patients age ≥45 years had a disproportionately high rate of bone TB, while foreign-born patients had increased pleural TB and HIV+ patients had increased meningeal TB. Age ≥45 years, HIV+ status, excessive alcohol use within the past 12 months, ESRD, and abnormal chest radiographs were independent risk factors for EPTB mortality during TB treatment. The epidemiologic risk factors identified by multivariate analyses provide new information that may be useful to health professionals in managing patients with EPTB.
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Affiliation(s)
- Xu Qian
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, P. R. China
- Center for Precision Biomedicine, Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
- People's Hospital of Hangzhou Medical College, Hangzhou, P. R. China
| | - Duc T Nguyen
- Houston Methodist Research Institute, Houston, TX, USA
| | - Jianxin Lyu
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, P. R. China
- People's Hospital of Hangzhou Medical College, Hangzhou, P. R. China
| | - Andreas E Albers
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Xiaohong Bi
- Center for Precision Biomedicine, Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
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Juno JA, Waruk JLM, Wragg KM, Mesa C, Lopez C, Bueti J, Kent SJ, Ball TB, Kiazyk SA. Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease. Front Immunol 2018; 9:1076. [PMID: 29868028 PMCID: PMC5967229 DOI: 10.3389/fimmu.2018.01076] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/30/2018] [Indexed: 12/17/2022] Open
Abstract
Background End-stage renal disease (ESRD) is associated with an increased susceptibility to infectious diseases, including infection with Mycobacterium tuberculosis (Mtb). Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites produced by many bacterial species, including Mtb, and may play an important role in providing protective immunity against tuberculosis infection in the lung. To date, little is known about MAIT cell frequency, phenotype, or function in ESRD patients. Methods MAIT cells, identified by surface marker expression or MR1 tetramer binding, were characterized in 20 ESRD and 20 healthy control participants by multicolor flow cytometry. Ex vivo MAIT cell phenotype and cytokine production following PMA/ionomycin, IL-12/IL-18, or Escherichia coli stimulation were determined. Monocyte phenotype and plasma C-reactive protein/inflammatory cytokine levels were quantified by flow cytometry, ELISA, and multiplex bead array. Results Peripheral blood MAIT cells were significantly depleted among ESRD patients compared to controls by both phenotypic and tetramer analysis and exhibited a loss of CXCR3 expression coupled to increased expression of CCR6 and CXCR6. ESRD was also associated with a shift in MAIT PMA-induced cytokine production away from IFNγ production and toward granulocyte macrophage-colony stimulating factor (GM-CSF) secretion, and a loss of E. coli-stimulated tumor necrosis factor α expression. Loss of IFNγ expression was associated with a combination of age, alterations in Tbet and Eomes expression, and inflammatory plasma cytokine levels. Conclusion The loss of peripheral blood MAIT cells and associated shifts in tissue homing receptor expression and GM-CSF production may contribute to an immune environment that is permissive to bacterial replication, particularly in the lungs.
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Affiliation(s)
- Jennifer A Juno
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.,Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Jillian L M Waruk
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada
| | - Kathleen M Wragg
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Christine Mesa
- National Laboratory for HIV Immunology, HIV/TB Co-Infection Unit, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Carmen Lopez
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada
| | - Joe Bueti
- Renal Program, Health Sciences Centre, Winnipeg, MB, Canada
| | - Stephen J Kent
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.,Melbourne Sexual Health Centre, Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC, Australia.,ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, VIC, Australia
| | - T Blake Ball
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.,National Laboratory for HIV Immunology, HIV/TB Co-Infection Unit, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Sandra A Kiazyk
- Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.,National Laboratory for HIV Immunology, HIV/TB Co-Infection Unit, Public Health Agency of Canada, Winnipeg, MB, Canada
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Hayward S, Harding RM, McShane H, Tanner R. Factors influencing the higher incidence of tuberculosis among migrants and ethnic minorities in the UK. F1000Res 2018; 7:461. [PMID: 30210785 PMCID: PMC6107974 DOI: 10.12688/f1000research.14476.2] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2018] [Indexed: 12/17/2022] Open
Abstract
Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB) compared with the general population. Historically, much of the disparity in incidence between UK-born and migrant populations has been attributed to differential pathogen exposure, due to migration from high-incidence regions and the transnational connections maintained with TB endemic countries of birth or ethnic origin. However, focusing solely on exposure fails to address the relatively high rates of progression to active disease observed in some populations of latently infected individuals. A range of factors that disproportionately affect migrants and ethnic minorities, including genetic susceptibility, vitamin D deficiency and co-morbidities such as diabetes mellitus and HIV, also increase vulnerability to infection with
Mycobacterium tuberculosis (M.tb) or reactivation of latent infection. Furthermore, ethnic socio-economic disparities and the experience of migration itself may contribute to differences in TB incidence, as well as cultural and structural barriers to accessing healthcare. In this review, we discuss both biological and anthropological influences relating to risk of pathogen exposure, vulnerability to infection or development of active disease, and access to treatment for migrant and ethnic minorities in the UK.
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Affiliation(s)
- Sally Hayward
- St John's College, University of Oxford, Oxford, OX1 3JP, UK
| | | | - Helen McShane
- The Jenner Institute, University of Oxford, Oxford, OX1 3PS, UK
| | - Rachel Tanner
- The Jenner Institute, University of Oxford, Oxford, OX1 3PS, UK
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Hayward S, Harding RM, McShane H, Tanner R. Factors influencing the higher incidence of tuberculosis among migrants and ethnic minorities in the UK. F1000Res 2018; 7:461. [PMID: 30210785 PMCID: PMC6107974 DOI: 10.12688/f1000research.14476.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2018] [Indexed: 09/04/2023] Open
Abstract
Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB) compared with the general population. Historically, much of the disparity in incidence between UK-born and migrant populations has been attributed to differential pathogen exposure, due to migration from high-incidence regions and the transnational connections maintained with TB endemic countries of birth or ethnic origin. However, focusing solely on exposure fails to address the relatively high rates of progression to active disease observed in some populations of latently infected individuals. A range of factors that disproportionately affect migrants and ethnic minorities, including genetic susceptibility, vitamin D deficiency and co-morbidities such as diabetes mellitus and HIV, also increase vulnerability to infection with Mycobacterium tuberculosis (M.tb) or reactivation of latent infection. Furthermore, ethnic socio-economic disparities and the experience of migration itself may contribute to differences in TB incidence, as well as cultural and structural barriers to accessing healthcare. In this review, we discuss both biological and anthropological influences relating to risk of pathogen exposure, vulnerability to infection or development of active disease, and access to treatment for migrant and ethnic minorities in the UK.
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Affiliation(s)
- Sally Hayward
- St John’s College, University of Oxford, Oxford, OX1 3JP, UK
| | | | - Helen McShane
- The Jenner Institute, University of Oxford, Oxford, OX1 3PS, UK
| | - Rachel Tanner
- The Jenner Institute, University of Oxford, Oxford, OX1 3PS, UK
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Cobelens F, Nagelkerke N, Fletcher H. The convergent epidemiology of tuberculosis and human cytomegalovirus infection. F1000Res 2018; 7:280. [PMID: 29780582 PMCID: PMC5934687 DOI: 10.12688/f1000research.14184.2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/23/2018] [Indexed: 12/28/2022] Open
Abstract
Although several factors are known to increase the risk of tuberculosis, the occurrence of tuberculosis disease in an infected individual is difficult to predict. We hypothesize that active human cytomegalovirus infection due to recent infection, reinfection or reactivation plays an epidemiologically relevant role in the aetiology of tuberculosis by precipitating the progression from latent tuberculosis infection to disease. The most compelling support for this hypothesis comes from the striking similarity in age-sex distribution between the two infections, important because the age-sex pattern of tuberculosis disease progression has not been convincingly explained. Cytomegalovirus infection and tuberculosis have other overlapping risk factors, including poor socio-economic status, solid organ transplantation and, possibly, sexual contact and whole blood transfusion. Although each of these overlaps could be explained by shared underlying risk factors, none of the epidemiological observations refute the hypothesis. If this interaction would play an epidemiologically important role, important opportunities would arise for novel approaches to controlling tuberculosis.
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Affiliation(s)
- Frank Cobelens
- Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Meibergdreef 9, AZ, Amsterdam, 1105, Netherlands
| | - Nico Nagelkerke
- Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB , R3E 0J9, Canada
| | - Helen Fletcher
- TB Centre, London School of Hygiene & Tropical Medicine, Keppel Street , London , WC1E 7HT, UK
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48
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Cobelens F, Nagelkerke N, Fletcher H. The convergent epidemiology of tuberculosis and human cytomegalovirus infection. F1000Res 2018; 7:280. [PMID: 29780582 PMCID: PMC5934687 DOI: 10.12688/f1000research.14184.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/01/2018] [Indexed: 03/25/2024] Open
Abstract
Although several factors are known to increase the risk of tuberculosis, the occurrence of tuberculosis disease in an infected individual is difficult to predict. We hypothesize that active human cytomegalovirus infection due to recent infection, reinfection or reactivation plays an epidemiologically relevant role in the aetiology of tuberculosis by precipitating the progression from latent tuberculosis infection to disease. The most compelling support for this hypothesis comes from the striking similarity in age-sex distribution between the two infections, important because the age-sex pattern of tuberculosis disease progression has not been convincingly explained. Cytomegalovirus infection and tuberculosis have other overlapping risk factors, including poor socio-economic status, sexual contact, whole blood transfusion and solid organ transplantation. Although each of these overlaps could be explained by shared underlying risk factors, none of the epidemiological observations refute the hypothesis. If this interaction would play an epidemiologically important role, important opportunities would arise for novel approaches to controlling tuberculosis.
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Affiliation(s)
- Frank Cobelens
- Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, Meibergdreef 9, AZ, Amsterdam, 1105, Netherlands
| | - Nico Nagelkerke
- Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB , R3E 0J9, Canada
| | - Helen Fletcher
- TB Centre, London School of Hygiene & Tropical Medicine, Keppel Street , London , WC1E 7HT, UK
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Ng Y, Aros-Atolagbe R, Ravanan R, Kendall C, Bovill B. Malignant metastatic deposits in an immunocompromised patient—could this be tuberculosis? Oxf Med Case Reports 2017; 2017:omx007. [PMID: 28775851 PMCID: PMC5534023 DOI: 10.1093/omcr/omx007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2016] [Revised: 01/09/2017] [Accepted: 02/16/2017] [Indexed: 11/14/2022] Open
Abstract
We report the case of a 50-year-old female renal transplant patient who developed disseminated deposits initially diagnosed as metastatic malignancy of unknown primary. She declined a tissue diagnosis but subsequently developed recurrent sepsis and symptomatic unilateral pleural effusion. Mycobacterium tuberculosis was cultured from pleural fluid. Following introduction of anti-tuberculous medications, her symptoms improved rapidly and the progression of her disseminated deposits stabilized. Tuberculosis is well-known to be associated with immunocompromised patients. It is a curable disease and should remain an important differential diagnosis for transplant patients who develop suspicious malignant metastatic lesions.
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Affiliation(s)
- Y Ng
- Department of Infectious Diseases, Southmead Hospital, Bristol, UK
- Correspondence address. Department of Infectious Diseases, Southmead Hospital, Bristol BS10 5NB, UK. E-mail:
| | | | - R Ravanan
- Department of Renal and Transplant Medicine, Southmead Hospital, Bristol, UK
| | - C Kendall
- Department of Palliative Medicine, Southmead Hospital, Bristol, UK
| | - B Bovill
- Department of Infectious Diseases, Southmead Hospital, Bristol, UK
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50
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Hamadah AM, Beaulieu LM, Wilson JW, Aksamit TR, Gregoire JR, Williams AW, Dillon JJ, Albright RC, Onuigbo M, Iyer VK, Hickson LJ. Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions. Nephron Clin Pract 2016; 132:198-206. [PMID: 26859893 DOI: 10.1159/000444148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 01/19/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The incidence of tuberculosis (TB) in end-stage renal disease is significantly higher than that in the general population. Among those with kidney dysfunction, anti-TB treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim: To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for TB, we conducted a case series (n = 12) of patients receiving maintenance hemodialysis (HD) from Mayo Clinic Dialysis Services and concurrent drug therapy for TB from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department (ED) visits independent of hospital admission) was compared before and during treatment. RESULTS Patients were treated for latent (n = 7) or active (n = 5) TB. The majority of patients with latent disease were treated with isoniazid (n = 5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-TB drug toxicities were described. More than half (58%) of the patients were hospitalized at least once. No ED or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre 0 vs. post 1). CONCLUSIONS Among HD patients, anti-TB therapy is associated with frequently reported symptoms and increased healthcare utilization. Among this subset, patients receiving treatment for latent disease may be those with greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations.
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Affiliation(s)
- Abdurrahman M Hamadah
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minn., USA
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